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Internal tandem duplication of fms-like tyrosine kinase 3 is associated with poor outcome in patients with myelodysplastic syndrome.
Cancer. 2004 Sep 01; 101(5):989-98.C

Abstract

BACKGROUND

The prognostic significance of internal tandem duplication (ITD) of the fms-like tyrosine kinase 3 gene (FLT3) for patients with myelodysplastic syndrome (MDS) is not clearly defined. In the current study, the authors sought to assess the value of FLT3/ITD mutation status as a prognostic genetic marker for patients with MDS.

METHODS

FLT3/ITD mutation status was evaluated by performing DNA polymerase chain reaction assays on 198 bone marrow samples obtained from patients with MDS at initial diagnosis. All aberrant products were sequenced, and GeneScan analysis was performed to measure FLT3/ITD mutant levels.

RESULTS

Five patients (2.5%)--2 of the 99 patients who had refractory anemia with excess blasts and 3 of the 51 patients who had chronic myelomonocytic leukemia--had FLT3/ITD mutations. FLT3/ITD was not observed in any of the 48 patients who had refractory anemia (with or without ringed sideroblasts). There was no significant difference in clinicohematologic characteristics, cytogenetic characteristics, or International Prognostic Scoring System score between the FLT3/ITD-positive group and the FLT3/ITD-negative group. Four of the 5 patients carrying the FLT3/ITD mutation experienced progression of disease to acute myeloid leukemia (AML), compared with 70 of the 193 patients who did not have FLT3/ITD (P = 0.066). In addition, progression to AML was more rapid in patients with FLT3/ITD-positive disease than in patients with FLT3/ITD-negative disease (mean +/- standard error, 3.0 +/- 0.5 months vs. 62.8 +/- 5.6 months; P < 0.0001). Patients with FLT3/ITD-positive disease also had significantly shorter survival compared with patients who had FLT3/ITD-negative disease (mean +/- standard error, 5.2 +/- 1.4 months vs. 33.7 +/- 3.1 months; P < 0.0001). On multivariate analysis, FLT3/ITD was identified as an independent predictor of reduced time to development of AML (P = 0.0001) and reduced overall survival (P = 0.002).

CONCLUSIONS

The results of the current study demonstrate that FLT3/ITD is associated with a high risk of transformation to AML, rapid progression of AML, and poor survival in patients with MDS.

Authors+Show Affiliations

Shih LY
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan. sly7012@adm.cgmh.org.tw
Lin TL
No affiliation info available
Wang PN
No affiliation info available
Wu JH
No affiliation info available
Dunn P
No affiliation info available
Kuo MC
No affiliation info available
Huang CF
No affiliation info available

MeSH

AdultAgedBone MarrowCell Transformation, NeoplasticDisease ProgressionFemaleGene DuplicationHumansLeukemia, Myelomonocytic, AcuteLeukemia, Myelomonocytic, ChronicMaleMiddle AgedMutationMyelodysplastic SyndromesPrognosisProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReceptors, Cell SurfaceRisk FactorsSurvival RateTandem Repeat SequencesTreatment Outcomefms-Like Tyrosine Kinase 3

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15329908

Citation

Shih, Lee-Yung, et al. "Internal Tandem Duplication of Fms-like Tyrosine Kinase 3 Is Associated With Poor Outcome in Patients With Myelodysplastic Syndrome." Cancer, vol. 101, no. 5, 2004, pp. 989-98.
Shih LY, Lin TL, Wang PN, et al. Internal tandem duplication of fms-like tyrosine kinase 3 is associated with poor outcome in patients with myelodysplastic syndrome. Cancer. 2004;101(5):989-98.
Shih, L. Y., Lin, T. L., Wang, P. N., Wu, J. H., Dunn, P., Kuo, M. C., & Huang, C. F. (2004). Internal tandem duplication of fms-like tyrosine kinase 3 is associated with poor outcome in patients with myelodysplastic syndrome. Cancer, 101(5), 989-98.
Shih LY, et al. Internal Tandem Duplication of Fms-like Tyrosine Kinase 3 Is Associated With Poor Outcome in Patients With Myelodysplastic Syndrome. Cancer. 2004 Sep 1;101(5):989-98. PubMed PMID: 15329908.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Internal tandem duplication of fms-like tyrosine kinase 3 is associated with poor outcome in patients with myelodysplastic syndrome. AU - Shih,Lee-Yung, AU - Lin,Tung-Liang, AU - Wang,Po-Nan, AU - Wu,Jin-Hou, AU - Dunn,Po, AU - Kuo,Ming-Chung, AU - Huang,Chein-Fuang, PY - 2004/8/27/pubmed PY - 2004/9/29/medline PY - 2004/8/27/entrez SP - 989 EP - 98 JF - Cancer JO - Cancer VL - 101 IS - 5 N2 - BACKGROUND: The prognostic significance of internal tandem duplication (ITD) of the fms-like tyrosine kinase 3 gene (FLT3) for patients with myelodysplastic syndrome (MDS) is not clearly defined. In the current study, the authors sought to assess the value of FLT3/ITD mutation status as a prognostic genetic marker for patients with MDS. METHODS: FLT3/ITD mutation status was evaluated by performing DNA polymerase chain reaction assays on 198 bone marrow samples obtained from patients with MDS at initial diagnosis. All aberrant products were sequenced, and GeneScan analysis was performed to measure FLT3/ITD mutant levels. RESULTS: Five patients (2.5%)--2 of the 99 patients who had refractory anemia with excess blasts and 3 of the 51 patients who had chronic myelomonocytic leukemia--had FLT3/ITD mutations. FLT3/ITD was not observed in any of the 48 patients who had refractory anemia (with or without ringed sideroblasts). There was no significant difference in clinicohematologic characteristics, cytogenetic characteristics, or International Prognostic Scoring System score between the FLT3/ITD-positive group and the FLT3/ITD-negative group. Four of the 5 patients carrying the FLT3/ITD mutation experienced progression of disease to acute myeloid leukemia (AML), compared with 70 of the 193 patients who did not have FLT3/ITD (P = 0.066). In addition, progression to AML was more rapid in patients with FLT3/ITD-positive disease than in patients with FLT3/ITD-negative disease (mean +/- standard error, 3.0 +/- 0.5 months vs. 62.8 +/- 5.6 months; P < 0.0001). Patients with FLT3/ITD-positive disease also had significantly shorter survival compared with patients who had FLT3/ITD-negative disease (mean +/- standard error, 5.2 +/- 1.4 months vs. 33.7 +/- 3.1 months; P < 0.0001). On multivariate analysis, FLT3/ITD was identified as an independent predictor of reduced time to development of AML (P = 0.0001) and reduced overall survival (P = 0.002). CONCLUSIONS: The results of the current study demonstrate that FLT3/ITD is associated with a high risk of transformation to AML, rapid progression of AML, and poor survival in patients with MDS. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/15329908/Internal_tandem_duplication_of_fms_like_tyrosine_kinase_3_is_associated_with_poor_outcome_in_patients_with_myelodysplastic_syndrome_ DB - PRIME DP - Unbound Medicine ER -